{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:34Z","timestamp":1787028574451,"version":"build-2736575974"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T00:00:00Z","timestamp":1759795200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["SC1GM111172"],"award-info":[{"award-number":["SC1GM111172"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R25GM069621"],"award-info":[{"award-number":["R25GM069621"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["U54MD007592"],"award-info":[{"award-number":["U54MD007592"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Misregulation of C-C chemokine receptor 7 (CCR7) has been linked to multiple autoimmune diseases including systemic lupus erythematosus, multiple sclerosis, and ankylosing spondylitis. As a G-protein-coupled receptor, located on the cell membrane, CCR7 can be targeted by inhibiting one of its two ligands, C-C chemokine ligand 19 (CCL19), to regulate its function. In this study, we examined signaling events downstream of CCL19 binding that provide a mechanism for regulation of the immune response. We used a CCR7 antagonist, CCL198-83, in immune studies in vivo, as a platform for a pharmaceutical to define the molecular events that are involved in regulating the humoral adaptive immune response. We found that in the presence of a T-cell-dependent antigen, C57BL\/6 mice treated during antigen exposure with CCL198-83 generated significantly higher levels of IgG1, the dominant isotype in extracellular bacterial infections that can activate complement, and IgG2c, the dominant isotype during viral and intracellular bacterial infections. Inhibiting ERK5 signaling downstream of CCR7 activation by CCL19, or disruption of CCL19 expression in CCL19\u2212\/\u2212 mice, also resulted in higher levels of IgG1 when compared to control mice. Differences in levels of IL-4 or other cytokines or lymphocyte types between wild-type and ERK5-deficient T cells did not account for antibody levels. Since pertussis-toxin-induced inhibition of lymphocyte chemotaxis is linked to elevated levels of IgG, we examined the effect of ERK5 on chemotaxis to CCR7 ligand CCL19. We found that disruption of ERK5 in T cells, or global disruption of CCL19 or CCR7, inhibited chemotaxis of T cells to CCL19, a mechanism that enhances sensitization during the exposure to an immunogen. Since CCR7 and its ligands have been linked to autoimmunity, these studies may provide insight into mechanisms that can be targeted to control autoimmune responses.<\/jats:p>","DOI":"10.3390\/ijms26199744","type":"journal-article","created":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T10:48:07Z","timestamp":1759834087000},"page":"9744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Signaling via C-C Chemokine Ligand 19 and Extracellular Regulated Kinase 5 in T Cells Limits the Humoral Adaptive Immune Response in Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Jaisel A.","family":"Cervantes","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Paul","family":"Welch","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Molecular Genetics and Immunology, The University of Kansas Medical Center, Kansas City, KS 66103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Kaiser","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Molecular Genetics and Immunology, The University of Kansas Medical Center, Kansas City, KS 66103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Bill","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA"},{"name":"Department of Microbiology, Molecular Genetics and Immunology, The University of Kansas Medical Center, Kansas City, KS 66103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-6935-8847","authenticated-orcid":false,"given":"Angel","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth L.","family":"Bill","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0645-0363","authenticated-orcid":false,"given":"Colin A.","family":"Bill","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7902-8713","authenticated-orcid":false,"given":"Charlotte M.","family":"Vines","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX 79968, USA"},{"name":"Department of Microbiology, Molecular Genetics and Immunology, The University of Kansas Medical Center, Kansas City, KS 66103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"110431","DOI":"10.1016\/j.intimp.2023.110431","article-title":"CCL21\/CCR7 axis as a therapeutic target for autoimmune diseases","volume":"121","author":"Han","year":"2023","journal-title":"Int. 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